Boron neutron capture therapy (BNCT) for the treatment of mammalian tumors (e.g. cancerous tumor cells) is based on the nuclear reaction between thermal neutrons and boron-10 to yield alpha particles and lithium-7 nuclei: ##STR1##
The high linear energy transfer (LET) alpha particles released in this nuclear reaction have a range in tissue of about 10 .mu.m, approximately equal to the diameter of a single cell. Their destructive effect is, therefore, highly localized to boron-loaded tissue. A key requirement of BNCT is the selective delivery of an adequate concentration of boron-10 to tumors (15-30 .mu.g .sup.10 B/g tumor). The lack of boron compounds with the requisite biological properties has been a major limitation for the clinical use of BNCT. Boronated analogues of compounds that are known to localize in various tumors (amino acids, thioruracils, chlorpromazine, nucleosides, antibodies, etc.) have been the focus of compound development in this area. The rationale for the synthesis of boron-containing nucleosides is that such structures would be conserved by rapidly proliferating tumor cells and phosphorylated by cellular kinases to mononucleotides. These may persist "locked-in" within the tumor cell or possibly be converted to the active precursors of nucleic acids, the di- and triphosphate forms.
A recent review article on BNCT can be found in Cancer Research, 50, 1061-1070, Feb. 15, 1990, "Boron Neutron Capture Therapy of Cancer", Rolf F. Barth, Albert H. Soloway and Ralph G. Fairchild. Another more recent review is in Scientific American, October 1990, Vol. 262, No. 10, pp. 100-107, "Boron Neutron Capture Therapy for Cancer", Rolf F. Barth et al. This latest review on pages 106-107 in its penultimate and ultimate columns speaks of BNCT treatments reported by Yutaka Mishima and his associates, including working with Duroc pigs and injecting a boron compound around a skin-level melanoma, following with exposure to thermal neutrons, and after several months noting that the melanomas began to shrink and eventually disappeared (apparently also reported in The Journal of Investigative Dermatology, Vol. 92, No. 5, Supplement, May 1989, 321S-325S). The "Scientific American" review in the paragraph bridging pages 106-107 also reports achieving through BNCT of a cure of primary melanomas on two patients.
The first mentioned review (i.e. Cancer Research, supra) on page 1063 in Table 1 tabulates some current boron compounds either being used or potentially useful as capture agents for BNCT therapy. Included in that tabulation is a 5-borono-2'-deoxy uridine, which compound contains a single B atom linked to its nuclei acid moiety of the nucleoside.